Peptides have an important signalling function and coordinate many biochemical processes. Therefore, peptides became essential and promising active ingredients especially in the cosmetic industry where compounds able to beautify the skin and its appendages, i.e. to improve their general condition, are always sought.
The present inventors were more particularly interested in searching for new peptides with activities on key molecules constituting the extracellular matrix (ECM) which decrease with age, particularly peptides active in the synthesis of collagen I and elastin and also active in the synthesis of glycoproteins like fibronectin.
Loss of density and thickness of the dermis is related to a reduction of the synthesis of macromolecules during aging by dermal fibroblasts, the cells responsible for their production. Collagen I is the most abundant protein in the dermis, essential to have a firm skin. Elastin is synthesized and secreted inside the dermal extracellular space. It is the major component of the elastic fibers (up to 90%).
Fibronectin is a glycoprotein present in the extracellular matrix, which plays a key role in cell adhesion to the extracellular matrix. It can simultaneously bind to the cell and to other molecules of the extracellular matrix, such as collagen or another molecule of fibronectin. Therefore, the molecules of fibronectin combine to form adhesive elastic fibers on the surface of many cells. This determines the mechanical properties (elasticity, flexibility, suppleness and firmness) of the skin.
The increase of collagen IV and laminins is also sought. It helps to restore/enhance the dermal/epidermal junction (DEJ). Collagen IV forms a two-dimensional network and is one of the major components of the DEJ. Laminins are also contained in the basal layer and involved in anchoring cells to the basal layer.
These two essential components of the DEJ provide together a better anchoring of the keratinocytes of the basal layer and help maintaining the flexibility and suppleness of the epidermis.
The reduction of protein synthesis with age becomes apparent at the level of the DEJ. Collagen IV is more fragmented and at the same time less produced, as well as laminins, which results in impaired JDE in some areas and poorer communication between melanocytes, keratinocytes and DEJ, and a reduced flexibility and suppleness of the system. The interest of stimulation of the synthesis of these two proteins thus clearly appears.
Results on the beautifying of skin and its general condition will be obtained thanks to the stimulation of the synthesis of these molecules, mainly results obtained at the level of the mechanical properties: a denser, more plumped, firmer, toned, supple and elastic skin, the peptide having a volumizing, plumping effect and thus an anti-wrinkle action.
Many peptides or peptide mixtures having properties on the MEC and anti-aging applications have been already proposed, including by the applicant, like the Pal-KTTKS (SEQ ID NO 1) marketed under the trademark MATRIXYL™, the mixture comprising Pal-GHK and Pal-GQPR (SEQ ID NO 2) under the trademark MATRIXYL™ 3000 or more recently the Pal-KMO2K under the tradename MATRIXYL Synthe-6™ (MO2 corresponding to a dioxygenated methionine). Other known peptides are mentioned in the following description.
Furthermore, patent application WO 2010/071132 discloses a series of eight peptides (-tri, -tetra, penta and hexa-peptides) derived from fermented milk and having been selected because they are not diggested by enzymes of the digestive tube and because they are able to penetrate the epithelial cells of the intestine. The authors further showed that at concentrations of about 40 ppm a stimulation of collagen synthesis and an increase in the proliferation of epidermal cells were observed. Due to these properties, the authors recommend that these peptides, naturally extracted or synthesized, could be advantageously ingested as oral cosmetics having anti-aging properties. The eight peptides have a PP (Pro-Pro) sequence: (Asn-Ile-Pro-Pro-Leu (NIPPL; SEQ ID NO 3), Ile-Pro-Pro (IPP), Ile-Pro-Pro-Leu (IPPL; SEQ ID NO 4), Val-Pro-Pro (VPP), Val-Pro-Pro-Phe (VPPF; SEQ ID NO 5), Pro-Val-Val-Val-Pro-Pro (PVVVPP; SEQ ID NO 6), Phe-Pro-Pro-Gln (FPPQ; SEQ ID NO 7) and Leu-Pro-Pro-Thr (LPPT; SEQ ID NO 8) and among them two peptides (the tetrapeptide IPPL (SEQ ID NO 4) and the pentapeptide NIPPL (SEQ ID NO 3)) comprise the more precise aminoacid sequence PPL. The NIPPL (SEQ ID NO 3) is presented as the prefered peptide with a better result in collagen production by fibroblastes: about +30% with regard to the control for a concentration of about 55 ppm, while only about +10% with regard to the control for a concentration of about 44 ppm for the IPPL peptide (SEQ ID NO 4).
EP 0 464 009 discloses oligopeptides derivatives of hypoxanthine and in particular the peptide hypoxanthine-PPR (hypoxanthine being the 6-hydroxypurine aralkyle radical) endowed with immunomodulating activity and pharmaceutical compositions containing them.
The aim of the present invention is to provide other peptides capable of improving the general condition of the skin and appendages, and more particularly peptides active on the synthesis of ECM proteins. In addition, it aims to provide sufficiently effective peptides that can be used alone or in combination, in amounts of a few ppm, and that can be used in the form of a topical composition, in particular a cosmetic composition.